title: An IL-1 cytokine member, IL-33, induces human basophil activation via its ST2 receptor.
abstract: Basophils are thought to play pivotal roles in allergic inflammation through rapid release of chemical mediators in addition to sustained production of Th2 cytokines, including IL-4. A newly identified cytokine, IL-33, has been recognized as one of the key cytokines enhancing Th2-balanced immune regulation through its receptor, ST2. The present study was conducted to elucidate whether IL-33 acts directly on, and affects the functions of, human basophils. Real-time PCR analysis showed that basophils express transcripts for ST2. The expression levels were significantly higher compared with eosinophils and neutrophils, and treatment with IL-33 significantly up-regulated basophil ST2 mRNA expression. Expressions of IL-4 and IL-13 mRNA were also up-regulated by IL-33, and there was also enhanced secretion of IL-4 protein. IL-33 increased the surface levels of basophil CD11b expression and enhanced basophil adhesiveness. Although IL-33 failed to directly induce degranulation or attract basophils, it exerted priming effects on basophils. It enhanced degranulation in response to IgE-crosslinking stimulus and also enhanced basophil migration toward eotaxin without changing surface CCR3. Also, IL-33 synergistically enhanced IL-4 production and CD11b expression by IL-3-stimulated basophils. Neutralization using Ab specific for ST2 significantly diminished the enhancing effects of IL-33 on both basophil CD11b expression and migration toward eotaxin, indicating that IL-33 signals via ST2 expressed on basophils. This study revealed that IL-33 potently regulates migration and activation of human basophils. IL-33 may be a key cytokine in the pathogenesis of Th2-dominant inflammation by acting not only on lymphocytes but also on effector cells such as basophils.
authors.affiliation: Department of Allergy and Rheumatology, University of Tokyo Graduate School of Medicine, Japan.
authors.forename: Maho
authors.initials: M
authors.lastname: Suzukawa
authors.forename: Motoyasu
authors.initials: M
authors.lastname: Iikura
authors.forename: Rikiya
authors.initials: R
authors.lastname: Koketsu
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Nagase
authors.forename: Chise
authors.initials: C
authors.lastname: Tamura
authors.forename: Akiko
authors.initials: A
authors.lastname: Komiya
authors.forename: Susumu
authors.initials: S
authors.lastname: Nakae
authors.forename: Kouji
authors.initials: K
authors.lastname: Matsushima
authors.forename: Ken
authors.initials: K
authors.lastname: Ohta
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Yamamoto
authors.forename: Masao
authors.initials: M
authors.lastname: Yamaguchi
mesh_terms: D015549:Basophil Degranulation Test / Q000379:methods; D001491:Basophils / Q000276:immunology* / Q000378:metabolism*; D002448:Cell Adhesion / Q000276:immunology; D002478:Cells, Cultured; D054413:Chemokine CCL11 / Q000378:metabolism; D002634:Chemotaxis, Leukocyte / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis; D005786:Gene Expression Regulation / Q000276:immunology; D006636:Histamine Release / Q000276:immunology*; D006801:Humans; D007375:Interleukin-1 / Q000378:metabolism / Q000502:physiology*; D000072179:Interleukin-1 Receptor-Like 1 Protein; D000067596:Interleukin-33; D007378:Interleukins / Q000378:metabolism / Q000502:physiology*; D012333:RNA, Messenger / Q000096:biosynthesis; D011956:Receptors, Cell Surface / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D017472:Receptors, Interleukin-1 / Q000502:physiology*
chemical_list: C515456:CCL11 protein, human; D054413:Chemokine CCL11; D016207:Cytokines; C079241:IL1RL1 protein, human; C506536:IL33 protein, human; D007375:Interleukin-1; D000072179:Interleukin-1 Receptor-Like 1 Protein; D000067596:Interleukin-33; D007378:Interleukins; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D017472:Receptors, Interleukin-1